萨拉毒素和内皮素-1血管收缩作用的构效关系

Structure-activity relationship in vasoconstrictor effects of sarafotoxins and endothelin-1.

作者信息

Kitazumi K, Shiba T, Nishiki K, Furukawa Y, Takasaki C, Tasaka K

机构信息

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.

出版信息

FEBS Lett. 1990 Jan 29;260(2):269-72. doi: 10.1016/0014-5793(90)80120-8.

DOI:10.1016/0014-5793(90)80120-8

PMID:2404800

Abstract

Sarafotoxins (SRTa, SRTb and SRTc) as well as endothelin-1 (ET-1) produced vasoconstrictions in rat thoracic aorta, rat isolated perfused mesentery and pithed rat in various of extents. The potency was ET-1 greater than SRTb greater than SRTa greater than SRTc at lower doses, but SRTb greater than ET-1 greater than SRTa greater than SRTc at higher doses. [Nitrophenylsulfenylated Trp21]SRTb and SRTb(1-19) caused no vasoconstriction. Either the reduction and carboxymethylation of Cys residues, the destruction of the intramolecular loop or the production of the non-natural disulfide bond, eliminated the constrictor activity. These results indicate that Trp21 and the intramolecular loop structure are essential, and Lys9 and Tyr13 may play some important roles for the vasoconstrictor activity of these peptides.

摘要

毒蜥毒素（SRTa、SRTb和SRTc）以及内皮素-1（ET-1）在不同程度上使大鼠胸主动脉、大鼠离体灌注肠系膜和脊髓横断大鼠产生血管收缩。在较低剂量时，效力顺序为ET-1大于SRTb大于SRTa大于SRTc，但在较高剂量时为SRTb大于ET-1大于SRTa大于SRTc。[硝基苯硫基化色氨酸21]SRTb和SRTb(1-19)未引起血管收缩。半胱氨酸残基的还原和羧甲基化、分子内环的破坏或非天然二硫键的产生均消除了收缩活性。这些结果表明，色氨酸21和分子内环结构是必不可少的，赖氨酸9和酪氨酸13可能对这些肽的血管收缩活性起一些重要作用。